2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl-propanoic acid, 1-methylethylester, also known as fenofibrate, is representative of a broad class of compounds having pharmaceutical utility as lipid-regulating drugs. More specifically, this compound is part of a lipid-regulating drug class of compounds commonly known as fibrates, and is disclosed in U.S. Pat. No. 4,058,552.
Fenofibrate has been prepared in several different formulations, c.f., U.S. Pat. Nos. 4,800,079 and 4,895,726. 4,895,726 discloses a co-micronized formulation of fenofibrate and a solid surfactant.
U.S. Pat. No. 4,961,890 discloses a process for preparing a controlled release formulation containing fenofibrate in an intermediate layer in the form of crystalline microparticles included within pores of an inert matrix. The formulation is prepared by a process involving the sequential steps of dampening said inert core with a solution based on said binder, then projecting said fenofibrate microparticles in a single layer onto said dampened core, and thereafter drying, before said solution based on said binder dissolves said fenofibrate microparticles, and repeating said three steps in sequence until said intermediate layer is formed.
European Patent Application No. EP0793958A2 discloses a process for producing a fenofibrate solid dosage form utilizing fenofibrate, a surface active drug and polyvinyl pyrrohidone in which the fenofibrate particles are mixed with a polyvinyl pyrrolidone solution. The thus obtained mixture is granulated with an aqueous solution of one or more surface active drugs, and the granules thus produced are dried.
PCT Publication No. W082/01649 discloses a fenofibrate formulation having granules that are comprised of a neutral core that is a mixture of saccharose and starch. The neutral core is covered with a first layer of fenofibrate, admixed with an excipient and with a second micropcrous outer layer of an edible polymer.
U.S. Pat. No. 5,645,856 discloses the use of a carrier for hydrophobic drugs, including fenofibrate, and pharmaceutical compositions based thereon. The carrier comprises a digestible oil and a pharmaceutically-acceptable surfactant component for dispersing the oil in vivo upon administration of the carrier, which comprises a hydrophilic surfactant, said surfactant component being such as not to substantially inhibit the in vivo lipolysis of the digestible oil.
U.S. Pat. No. 6,383,517 discloses a process for preparing a solid formulation of fenofibrate comprising dissolving the fenofibrate in a surfactant solution, premixing an excipient, wet granulating the mixture, drying the mixture and forming a finished dosage form.
The prior art processes obtain small particles of fenofibrate by the use of co-micronization steps and/or require the presence of surfactants. These processes result in formulations that may not have maximized dissolution characteristics, and may cause gastro intestinal irritation.
It is an object of the present invention to provide small particles of lipid regulating drugs, more preferably fenofibrate, having comparable dissolution and absorption characteristics to those particles of such drugs prepared by the prior art techniques without the need of micronizing the lipid-regulating drug or utilizing surfactants.